NM_005908.4(MANBA):c.1398G>A (p.Trp466Ter) AND Beta-D-mannosidosis

Clinical significance:Pathogenic (Last evaluated: Aug 5, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001194223.1

Allele description [Variation Report for NM_005908.4(MANBA):c.1398G>A (p.Trp466Ter)]

NM_005908.4(MANBA):c.1398G>A (p.Trp466Ter)

Gene:
MANBA:mannosidase beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q24
Genomic location:
Preferred name:
NM_005908.4(MANBA):c.1398G>A (p.Trp466Ter)
HGVS:
  • NC_000004.12:g.102664772C>T
  • NG_012804.1:g.101223G>A
  • NG_012804.2:g.101223G>A
  • NM_005908.4:c.1398G>AMANE SELECT
  • NP_005899.3:p.Trp466Ter
  • NC_000004.11:g.103585929C>T
  • NM_005908.3:c.1398G>A
Protein change:
W466*
Links:
dbSNP: rs1208178394
NCBI 1000 Genomes Browser:
rs1208178394
Molecular consequence:
  • NM_005908.4:c.1398G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Beta-D-mannosidosis (MANSB)
Synonyms:
Mannosidosis, beta A, lysosomal; Lysosomal beta-mannosidase deficiency; Beta-mannosidase deficiency
Identifiers:
MONDO: MONDO:0009562; MedGen: C4048196; Orphanet: 118; OMIM: 248510

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001363585Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Aug 5, 2019)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A MANBA mutation resulting in residual beta-mannosidase activity associated with severe leukoencephalopathy: a possible pseudodeficiency variant.

Sabourdy F, Labauge P, Stensland HM, Nieto M, Garcés VL, Renard D, Castelnovo G, de Champfleur N, Levade T.

BMC Med Genet. 2009 Sep 3;10:84. doi: 10.1186/1471-2350-10-84.

PubMed [citation]
PMID:
19728872
PMCID:
PMC2745377

Molecular analysis in two beta-mannosidosis patients: description of a new adult case.

Gort L, Duque J, Fabeiro JM, Zulaica A, Coll MJ, Chabás A.

Mol Genet Metab. 2006 Dec;89(4):398-400. Epub 2006 Aug 14.

PubMed [citation]
PMID:
16904924

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363585.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: MANBA c.1398G>A (p.Trp466X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A splice site variant downstream of this position has been classified as pathogenic by our laboratory (c.2158-2A>G). The variant allele was found at a frequency of 4e-06 in 251454 control chromosomes. c.1398G>A has been reported in the literature in at-least one individual affected with Beta-Mannosidosis (Gort_2006). At least one publication reports experimental evidence evaluating an impact on protein function (Gort_2006). The most pronounced variant effect results in <10% of normal activity. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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